Papillomaviruses are pathogenic viruses that can infect a wide variety of different species of animals that include humans. Papillomavirus infection is often characterized by the induction of epithelial and fibro-epithelial tumors, or warts at the site of infection. Each species of vertebrate is infected by a species-specific set of Papillomavirus. For example, more than one hundred different human papillomavirus (HPV) genotypes have been isolated to date. Papillomaviruses are highly species-specific infective agents. Canine and rabbit papillomaviruses are not known to induce papillomas in heterologous species such as humans. Immunity to infection against one papillomavirus type generally does not appear to confer immunity against another type, even when the types infect a homologous species.
Papillomaviruses cause genital warts, a prevalent sexually-transmitted disease in humans. HPV types 6 and 11 are most commonly associated with benign genital warts condylomata acuminata. Genital warts are very common, and subclinical or unapparent HPV infection is even more common than clinical infection. While most HPV-induced lesions are benign, lesions arising from certain papillomavirus types (e.g., HPV-16 and HPV-18) can undergo malignant progression to potentially lead to cervical cancer. Of the HPV genotypes involved in cervical cancer, HPV-16 is the most common, being found in about 50% of cervical cancers.
In view of the significant health risks posed by papillomavirus infection generally, and human papillomavirus infection in particular, various groups have reported the development of recombinant papillomavirus antigens and their use as diagnostic agents and as prophylactic vaccines. In general, such research has been focused toward producing prophylactic vaccines containing the major capsid protein (L1) alone or in combination with the minor capsid protein (L2).
Prophylactic vaccines currently in clinical trials are based upon VLPs (virus-like particles). VLPs are assemblies of 72 pentamers or capsomeres of the major papillomavirus capsid protein L1. However, these types of vaccines are relatively expensive to produce in that they require eukaryotic expression systems or complex purification, and are less stable than capsomere preparations. VLP vaccines may not provide cross protection against other papillomavirus serotypes, as neutralizing immune responses tend to be predominately type-specific.